EC-01-02: BI-DIRECTIONAL RELATIONSHIP BETWEEN CIRCADIAN RHYTHMS AND ALZHEIMER'S DISEASE PATHOLOGY

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

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Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer’s Disease: Preliminary Findings in a Pivotal Study

Frontiers in Physiology ◽

10.3389/fphys.2021.755322 ◽

2022 ◽

Vol 12 ◽

Author(s):

Riccardo Cremascoli ◽

Davide Sparasci ◽

Gianluca Giusti ◽

Stefania Cattaldo ◽

Elisa Prina ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms ◽

Sleep Quality ◽

Cognitive Functioning ◽

Light Exposure ◽

Light Therapy ◽

Circadian Phase ◽

Falling Asleep ◽

Mood And Cognition

It is shown that the circadian system is affected in patients with Alzheimer’s disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.

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Effects of aging and genotype on circadian rhythms, sleep, and clock gene expression in APPxPS1 knock-in mice, a model for Alzheimer's disease

Experimental Neurology ◽

10.1016/j.expneurol.2012.05.011 ◽

2012 ◽

Vol 236 (2) ◽

pp. 249-258 ◽

Cited By ~ 51

Author(s):

Marilyn J. Duncan ◽

J. Tyler Smith ◽

Kathleen M. Franklin ◽

Tina L. Beckett ◽

M. Paul Murphy ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms ◽

Clock Gene ◽

Clock Gene Expression ◽

Effects Of Aging

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Interacting influences of aging and Alzheimer's disease on circadian rhythms

European Journal of Neuroscience ◽

10.1111/ejn.14358 ◽

2019 ◽

Vol 51 (1) ◽

pp. 310-325 ◽

Cited By ~ 7

Author(s):

Marilyn J. Duncan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms

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Increased Light Exposure Consolidates Sleep and Strengthens Circadian Rhythms in Severe Alzheimer's Disease Patients

Behavioral Sleep Medicine ◽

10.1207/s15402010bsm0101_4 ◽

2003 ◽

Vol 1 (1) ◽

pp. 22-36 ◽

Cited By ~ 202

Author(s):

Sonia Ancoli-Israel ◽

Philip Gehrman ◽

Jennifer L. Martin ◽

Tamar Shochat ◽

Matthew Marler ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms ◽

Light Exposure

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Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population

GeroScience ◽

10.1007/s11357-021-00477-0 ◽

2021 ◽

Author(s):

Maria Giulia Bacalini ◽

Flavia Palombo ◽

Paolo Garagnani ◽

Cristina Giuliani ◽

Claudio Fiorini ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythm ◽

Circadian Rhythms ◽

Circadian Clock ◽

Successful Aging ◽

Clock Genes ◽

Association Studies ◽

Italian Population ◽

Age Related

AbstractMany physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.

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In Silico Analyses for Key Genes and Molecular Genetic Mechanism in Epilepsy and Alzheimer’s Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180724150839 ◽

2018 ◽

Vol 17 (8) ◽

pp. 608-617 ◽

Cited By ~ 11

Author(s):

Xiao-wen Jiang ◽

Hong-yuan Lu ◽

Ziru Xu ◽

Tian-yi Liu ◽

Qiong Wu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythms ◽

Differentially Expressed Genes ◽

Kegg Pathway ◽

Molecular Genetic ◽

Differentially Expressed ◽

Genetic Mechanism ◽

Pathway Enrichment ◽

Key Genes

Background: Epilepsy and Alzheimer's disease are common neuropathies with a complex pathogenesis. Both of them have some correlations in etiology, pathogenesis, pathological changes, clinical manifestations and treatment. Objective: This study investigated the key genes and molecular genetic mechanism in epilepsy and Alzheimer’s disease by bioinformatics analysis. Method: Two gene expression profiles were used to screen differentially expressed genes by GEO2R tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Then the protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software which can be used to analyze modules with MCODE. Results: A total of 199 differentially expressed genes (DEGs) in the two groups. According to GO_BP analysis and KEGG pathway enrichment by DAVID, we found DEGs referring to several pathways significantly down-regulated in endocytosis, such as endocytosis, synaptic vesicle cycle, lysosome, cAMP signaling pathway, circadian entrainment, LTP, glutamatergic synapse and GABAergic synapse pathway. The regulator genes of the upstream pathway of circadian rhythms were obviously downgraded. Conclusion: Our research demonstrated that the regulatory genes of the upstream pathway of circadian rhythms were obviously downgraded. These biological pathways and DEGs or hub genes may contribute to revealing the molecular relationship between Alzheimer's disease and epilepsy.

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